Establishment of a Humanized Mouse Model for Investigating Th2-Mediated Contact Hypersensitivity 4788

Abstract Description Contact hypersensitivity (CHS) is a severe dermatitis triggered by repeated exposure to specific antigens or haptens. While studies using wild-type mice have identified Th2 cells as key mediators of allergic CHS, their precise role in human CHS remains unclear due to the absence of a suitable human model. To address this, we developed a novel humanized mouse model by introducing the human IL-4 gene into NOG mice, promoting the abundant differentiation of human Th2 cells. PBMCs from healthy donors were transplanted into these mice, which were sensitized by subcutaneous oxazolone (OXA) administration. After the following week, OXA exposures three times a week, CHS was induced after seven times exposure. OXA painting led to T cell accumulation in the skin of NOG-hIL-4 Tg mice, whereas no accumulation was observed in MHC class I and II double knockout NOG-hIL-4 Tg mice, indicating the necessity of antigen presentation for this process. TCR repertoire analysis revealed that skin-accumulated T cell clones were distinct from those in the spleen, suggesting a specific immune response in dermatitis lesions. Moreover, treatment with the anti-IL-4R antibody Dupilumab completely suppressed CHS pathology, confirming the role of Th2 cells in disease induction. This model provides a valuable platform for investigating CHS mechanisms and developing therapeutic strategies. Funding Sources JSPS KAKENHI Grant Number JP22K06060 Topic Categories Immune Mechanisms of Human Disease (HUM)